1. Field of the Invention
The present invention relates to a microsensor for determination of glucose and other analytes in liquids based on affinity viscosimetry.
2. Description of the Related Art
Affinity sensors are important for analytics, as there exists a large number of affinity receptors, e.g. antibodies, which are not catalytically active. The technical task to transduce concentration dependent binding of analytes to the suitable receptor into an electrical signal within a microsensor, is an actual one, which is not easy to solve. A promising way for solving this task consists in the inclusion of receptor proteins and polymer affinity ligands in the lumen of a dialysis hollow fiber with a membrane which is permeable to the analyte (schultz, J. S. and Sims, G., 1979: Affinity sensors for individual metabolites, Biotechn. Bioeng. Symp-9, 65-71, Schultz, J. S., 1982, Optical sensor of plasma constituents, U.S. Pat. 4,344,438). The analyte-dependent dissociation of the receptor from the polymer ligand may be made detectable by diffusion of the polymer binding partner between the immobilized binding site and the ligand phase within the fiber lumen (Schultz, J. S., Mansouni, S. and Goldstein, I. J., 1982: Affinity sensor, A new technique for developing implantable sensor for glucose and other metabolites, Diabetes Care, 5,245-253, Knoll, D., Ehwald, K. E., Ehwald, R. Sorge, E., Ballersatdt, R. und Bolleroth, M., 1991: A silicon based microsystem for continuous in vivo glucose monitoring using a new reversible measuring principle) or by Fluorescence quenching (Meadows, D. L. and Schultz J. S., 1988, Fiberoptic bionsensor based on fluorescence energy transfer, Talante 35, 145-150). An interesting and simple alternative to the mentioned techniques is an affinity viscosimetry, measuring the concentration of affinity bonds mechanically in a direct manner. Affinity viscosimetry with dispersions of dextran and Concanavalin A is suitable for glucose determination in the blood sugar range and may be carried out with dialysis hollow fibers. The until now described hollow fiber viscosimeters do not have an electrical signal transducer and are unstable because of nonavoidable volume changes of the sensitive polymer phase (Ballerstadt, R. und Ehwald, R., 1992, Affinitatssensor, DE-P4203466, Ballerstadt, R., und Ehwald, R, 1994: Suitability of aqueous dispersion of dextran and Concanavalin A for glucose sensing in different variants of the affinity sensor, Biosensors and Bioelectronics, 9, 557-567).
An important field of application of microsensors is the on-line registration of analytes in body fluids, e.g. of glucose in the blood. Affinity viscosimetry is generally suitable for measuring relevant analytes which are known to bind to affinity receptor proteins. A miniaturized implantable affinity viscosimeter combined with a dialysis chamber or hollow fiber would therefore have promising applications. Such viscosimeter is not known.